tbuckley/cabot-search huggingface dataset:
Blinatumomab is associated with favorable outcomes in patients with B‐cell lineage acute lymphoblastic leukemia and positive measurable residual disease at a threshold of 10<sup>−4</sup> and higher
Authors: Elias J. Jabbour, Nicholas J. Short, Nitin Jain, Nadya Jammal, Jeffrey Jorgensen, Sa Wang, Xuemei Wang, Maro Ohanian, Yesid Alvarado, Tapan Kadia, Koji Sasaki, Rebecca Garris, Guillermo Garcia‐Manero, Farhad Ravandi, Hagop M. Kantarjian
Journal: American Journal of Hematology (2022)

The presence of measurable residual disease (MRD) is the strongest predictor of relapse in acute lymphoblastic leukemia (ALL). We conducted a prospective, single-arm, phase II study in adults with B-cell ALL with MRD ≥1 × 10-4 after ≥3 months from the start of frontline therapy or one month from any salvage therapy. Blinatumomab was administered at a standard dosing of 28 micrograms daily as a continuous infusion for up to five cycles and up to four additional maintenance cycles. Thirty-seven patients with a median age of 43 years (range, 22-84 years) were treated. Twenty-seven patients (73%) were treated in first complete remission (CR) and 10 patients (27%) in second CR and beyond. Eighteen patients (49%) had Philadelphia-chromosome positive ALL and received concomitant tyrosine kinase inhibitor therapy. Twenty-three patients (62%) had a baseline MRD ≥10-3 . A median of three cycles (range, 1-9 cycles) were administered. Overall, 27 patients (73%) achieved MRD-negative remission. With a median follow-up of 31 months (range, 5-70 months), the estimated 3-year relapse-free survival (RFS) rate was 63% (95% confidence interval [CI], 43%-77%) and overall survival (OS) rate 67% (95% CI, 46%-81%). These rates were 51% (95% CI, 27%-70%) and 61% (95% CI, 36%-78%) in patients with baseline MRD ≥1 × 10-3 , and 83% (95% CI, 45%-95%) and 77% (95% CI, 32%-95%) in patients with baseline MRD <10-3 respectively. The rates of adverse events were consistent with previous studies of blinatumomab. In summary, blinatumomab induced MRD negativity in most patients and resulted in high rates of RFS and OS. This study is registered at www.clinicaltrials.gov as #NCT02458014. Funding was provided by Amgen Inc.
Association Between Statin Use and Progression of Arterial Stiffness Among Adults With High Atherosclerotic Risk
Authors: Yan-Feng Zhou, Yanxiu Wang, Guodong Wang, Zhen Zhou, Shuohua Chen, Tingting Geng, Yan-Bo Zhang, Yi Wang, Jun-Xiang Chen, An Pan, Shouling Wu
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Limited studies have investigated the association between statin use and progression of arterial stiffness, a key player in the pathophysiology of cardiovascular disease. <h3>Objective</h3> To examine the association between statin use and progression of arterial stiffness in Chinese adults with high atherosclerotic risk measured by brachial-ankle pulse wave velocity (baPWV). <h3>Design, Setting, and Participants</h3> This retrospective cohort study enrolled 5105 adults with high atherosclerotic risk from the Kailuan General Hospital from 2010 to 2020. Data were analyzed from February 2021 to April 2022. <h3>Exposures</h3> Statin use information was retrieved from electronic medical records from 2010 to 2020, and statin users were those who have been prescribed any statin medications at least 6 months before baPWV measurements. Statin users were 1:1 matched with non–statin users by propensity score method. <h3>Main Outcomes and Measures</h3> Progression of baPWV was assessed using the absolute difference between baseline and follow-up baPWV, divided by the follow-up time in years. Multivariable linear regression models were used to estimate the association between statin use and arterial stiffness. <h3>Results</h3> Among 5105 adults with assessment of baPWV (mean [SD] age: 60.8 [9.7] years; 3842 [75.3%] men and 1263 [24.7%] women), 1310 statin users were matched with 1310 non–statin users (mean [SD] age, 63.2 [9.3] years). Compared with non–statin users, statin users were associated with significantly lower baPWV at baseline (difference: −33.6 cm/s; 95% CI, −62.1 to −5.1 cm/s). Among 1502 adults with repeated assessment of baPWV, 410 statin users were matched with 410 non–statin users (mean [SD] age, 62.9 [9.2] years). Compared with non–statin users, statin users had significantly slower progression of baPWV (difference, −23.3 cm/s per year; 95% CI, −40.6 to −6.0 cm/s per year) during a mean (SD) follow-up of 4.8 (2.7) years. A significantly slower progression of baPWV was observed in continuous statin users (difference, −24.2 cm/s per year; 95% CI, −42.2 to −6.3 cm/s per year) and high adherent users (difference, −39.7 cm/s per year; 95% CI, −66.9 to −12.4 cm/s per year), but not in discontinued users (difference, −17.3 cm/s per year; 95% CI, −52.4 to 17.8 cm/s per year) and low adherent users (difference, −17.9 cm/s per year; 95% CI, −36.5 to 0.7 cm/s per year), compared with non–statin users. <h3>Conclusions and Relevance</h3> In this cohort study, statin use was associated with slower progression of arterial stiffness in Chinese adults with high atherosclerotic risk.
Association of Insurance Status and Extent of Organ Involvement With Survival Among Patients With Stage IV Cancer
Authors: Peter L. Zhan, Maureen E. Canavan, Theresa Ermer, Matthew D. Pichert, Andrew X. Li, Richard C. Maduka, Daniel J. Boffa
Journal: JAMA Network Open (2022)

This cohort study examines the association of insurance status and extent of metastatic organ involvement with survival among patients with stage IV cancer to better understand outcome disparities in the US.
3P Identification of novel biomarkers of response to ATR inhibitors in ARID1A mutant ovarian clear cell carcinoma
Authors: J.R. Stewart, J. Baxter, D. Zatreanu, R. Brough, F. Song, A. Konde, D. Krastev, J. Alexander, R. Natrajan, S. Pettitt, S. Banerjee, C. Lord
Journal: Annals of Oncology (2022)
33P The development of infrastructure for mainstream ovarian cancer genetic testing (DEMO)
Authors: I.G. Funingana, E. Leung, M-L. Alcaraz, L. Bird, J.E. Ang, C. Parkinson, M. Jimenez-Linan, S. Freeman, C. Spencer, J. Winning, R. Ganesan, S. Williams, K.R. Ong, P. Abedin, S. Sundar, J. Balega, J.D. Brenton
Journal: Annals of Oncology (2022)
Microbial uptake in oral mucosa–draining lymph nodes leads to rapid release of cytotoxic CD8 <sup>+</sup> T cells lacking a gut-homing phenotype
Authors: Juliana Barreto de Albuquerque, Lukas M. Altenburger, Jun Abe, Diego von Werdt, Stefanie Wissmann, Jose Martínez Magdaleno, David Francisco, Geert van Geest, Xenia Ficht, Matteo Iannacone, Remy Bruggmann, Christoph Mueller, Jens V. Stein
Journal: Science Immunology (2022)

The gastrointestinal (GI) tract constitutes an essential barrier against ingested microbes, including potential pathogens. Although immune reactions are well studied in the lower GI tract, it remains unclear how adaptive immune responses are initiated during microbial challenge of the oral mucosa (OM), the primary site of microbial encounter in the upper GI tract. Here, we identify mandibular lymph nodes (mandLNs) as sentinel lymphoid organs that intercept ingested Listeria monocytogenes (Lm). Oral Lm uptake led to local activation and release of antigen-specific CD8 + T cells that constituted most of the early circulating effector T cell (T EFF ) pool. MandLN-primed T EFF disseminated to lymphoid organs, lung, and OM and contributed substantially to rapid elimination of target cells. In contrast to CD8 + T EFF generated in mesenteric LN (MLN) during intragastric infection, mandLN-primed T EFF lacked a gut-seeking phenotype, which correlated with low expression of enzymes required for gut-homing imprinting by mandLN stromal and dendritic cells. Accordingly, mandLN-primed T EFF decreased Lm burden in spleen but not MLN after intestinal infection. Our findings extend the concept of regional specialization of immune responses along the length of the GI tract, with CD8 + T EFF generated in the upper GI tract displaying homing profiles that differ from those imprinted by lymphoid tissue of the lower GI tract.
Epithelial HIF2α expression induces intestinal barrier dysfunction and exacerbation of arthritis
Authors: Jinming Wen, Pang Lyu, Iris Stolzer, Jin Xu, Andreas Gießl, Zhen Lin, Darja Andreev, Katerina Kachler, Rui Song, Xianyi Meng, Shan Cao, Giuliana Guggino, Francesco Ciccia, Claudia Günther, Georg Schett, Aline Bozec
Journal: Annals of the Rheumatic Diseases (2022)

To investigate how the mucosal barrier in the intestine influences the development of arthritis, considering that metabolic changes in the intestinal epithelium influence its barrier function.
Infectious Aortic Aneurysm in a Patient With Leriche Syndrome
Authors: Takashi Norikane, Yuka Yamamoto, Yasukage Takami, Ryosuke Tani, Yoshihiro Nishiyama
Journal: Clinical Nuclear Medicine (2022)

Leriche syndrome is a relatively rare atherosclerotic occlusive disease characterized by total occlusion of the abdominal aorta and/or both iliac arteries. The typical clinical manifestations of Leriche syndrome include intermittent claudication, fatigue, and leg pain. We present the case of a 56-year-old man with Leriche syndrome accompanied by an infectious abdominal aortic aneurysm. 18 F-FDG PET angiography/CT and 18 F-FDG PET/CT provided important information about the thrombus and infected sites.
DJ-1 governs airway progenitor cell/eosinophil interactions to promote allergic inflammation
Authors: Kuan Li, Qiuyang Zhang, Li Li, Shuangyan Li, Qing Yue, Xue Li, Yu Li, Jianhai Wang, Sisi Wang, Zengqiang Yuan, Huaiyong Chen
Journal: Journal of Allergy and Clinical Immunology (2022)
False Positive Ventilation/Perfusion SPECT/CT Mismatch Mimicking Pulmonary Embolism in a Patient With Bilateral Lung Transplant
Authors: Patrick Sandach, Björn Kleibrink, Sandra Maier, Ken Herrmann, Hubertus Hautzel
Journal: Clinical Nuclear Medicine (2022)

Ventilation/perfusion SPECT/CT has very high sensitivity with little false-positive findings for diagnosing pulmonary embolism (PE). However, bronchopulmonary tumors or structural changes of the lungs' vasculature infrequently mimic PE. Here, a 59-year-old man presented with acute dyspnea and acute renal failure 5 years after bilateral lung transplant. Pulmonary ventilation/perfusion SPECT/CT was performed demonstrating a lobar mismatch of the left upper lung lobe indicative for PE. Bronchoscopy revealed local hyperemia of this lobe, indicating prolonged venous blood return. Subsequent CT angiography confirmed postsurgical upper pulmonary vein obliteration as final diagnosis. In conclusion, pulmonary vein obliteration might cause false-positive ventilation/perfusion SPECT/CT.
Reactivation/relapse of SARS-CoV-2 in a child following haematopoietic stem cell transplantation, confirmed by whole genome sequencing, following apparent viral clearance
Authors: J Hatcher, E Gil, N Storey, JR Brown, JC Hartley, J Breuer, G Lucchini, K Rao, D O'Connor, H Dunn
Journal: Journal of Infection (2022)
ATP-sensitive potassium channels: A double-edged sword in neurodegenerative diseases
Authors: Jirong Lv, Xue Xiao, Mingxia Bi, Tingting Tang, Deao Kong, Meining Diao, Qian Jiao, Xi Chen, Chunling Yan, Xixun Du, Hong Jiang
Journal: Ageing Research Reviews (2022)
Fluorescence in situ hybridization for detecting Coxiella burnetii in tissue samples from chronic Q fever patients
Authors: Sheila B. Buijs, Jesper M. Weehuizen, Tim K. Jensen, Mette Boye, Mirjam HA. Hermans, Peet TGA. Nooijen, Andy IM. Hoepelman, Chantal P. Bleeker-Rovers, Jan Jelrik Oosterheert, Peter C. Wever
Journal: Clinical Microbiology and Infection (2022)

Detection of the intracellular bacterium Coxiella burnetii, causative agent of chronic Q fever, is notoriously difficult. Diagnosis of and duration of antibiotic treatment for chronic Q fever is partly determined by detection of the bacterium with polymerase chain reaction (PCR). Fluorescence in situ hybridization (FISH) might be a promising technique for detecting C. burnetii in tissue samples from chronic Q fever patients, but its value in comparison with PCR is uncertain. We aim to assess the value of FISH for detecting C. burnetii in tissue of chronic Q fever patients.FISH and PCR were performed on tissue samples from Dutch chronic Q fever patients collected during surgery or autopsy. Sensitivity, specificity, and overall diagnostic accuracy were calculated. Additionally, data on patient and disease characteristics were collected from electronic medical records.In total, 49 tissue samples from mainly vascular walls, heart valves, or placentas, obtained from 39 chronic Q fever patients, were examined by FISH and PCR. The sensitivity and specificity of FISH compared to PCR for detecting C. burnetii in tissue samples from chronic Q fever patients was 45.2% (95% confidence interval (CI), 27.3% - 64.0%) and 84.6% (95% CI, 54.6% - 98.1%), respectively. The overall diagnostic accuracy was 56.8% (95% CI, 42.2% - 72.3%). Two C. burnetii PCR negative placentas were FISH positive. Four FISH results (8.2%) were deemed inconclusive because of autofluorescence.With an overall diagnostic accuracy of 57.8%, we conclude that FISH has limited value in the routine diagnostics of chronic Q fever.
Neutrophil gelatinase-associated lipocalin is elevated in children with acute kidney injury and sickle cell anemia, and predicts mortality
Authors: Anthony Batte, Sahit Menon, John M. Ssenkusu, Sarah Kiguli, Robert Kalyesubula, Joseph Lubega, Zachary Berrens, Edrisa Ibrahim Mutebi, Rodney Ogwang, Robert O. Opoka, Chandy C. John, Andrea L. Conroy
Journal: Kidney International (2022)

Urine neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury that has been adapted to a urine dipstick test. However, there is limited data on its use in low-and-middle-income countries where diagnosis of acute kidney injury remains a challenge. To study this, we prospectively enrolled 250 children with sickle cell anemia aged two to 18 years encompassing 185 children hospitalized with a vaso-occlusive pain crisis and a reference group of 65 children attending the sickle cell clinic for routine care follow up. Kidney injury was defined using serial creatinine measures and a modified-Kidney Disease Improving Global Outcome definition for sickle cell anemia. Urine NGAL was measured using the NGAL dipstick and a laboratory reference. The mean age of children enrolled was 8.9 years and 42.8% were female. Among hospitalized children, 36.2% had kidney injury and 3.2% died. Measured urine NGAL levels by the dipstick were strongly correlated with the standard enzyme-linked immunosorbent assay for urine NGAL (hospitalized children, 0.71; routine care reference, 0.88). NGAL levels were elevated in kidney injury and significantly increased across injury stages. Hospitalized children with a high-risk dipstick test (300ng/mL and more) had a 2.47-fold relative risk of kidney injury (95% confidence interval 1.68 to 3.61) and 7.28 increased risk of death (95% confidence interval 1.10 to 26.81) adjusting for age and sex. Thus, urine NGAL levels were found to be significantly elevated in children with sickle cell anemia and acute kidney injury and may predict mortality.
When I use a word . . . . Counterfactual medical history: Milton’s treatment
Authors: Jeffrey K Aronson
Journal: BMJ (2022)

<h3>Abstract</h3> Comparative anatomy studies of the skull of archosaurs provide insights on the mechanisms of evolution for the morphologically and functionally diverse species of crocodiles and birds. One of the key attributes of skull evolution is the anatomical changes associated with the physical arrangement of cranial bones. Here, we compare the changes in anatomical organization and modularity of the skull of extinct and extant archosaurs using an Anatomical Network Analysis approach. We show that the number of bones, their topological arrangement, and modular organization can discriminate between birds, non-avian dinosaurs, and crurotarsans, and between extant and extinct species. By comparing within the same framework juveniles and adults for crown birds and alligator (<i>Alligator mississippiensis</i>), we find that adult and juvenile alligator skulls are topologically similar, whereas juvenile bird skulls have a morphological complexity and anisomerism more similar to that of non-avian dinosaurs and crurotarsans than to their adult forms. Clade-specific ontogenetic differences in skull organization, such as extensive postnatal fusion of cranial bones in crown birds, can explain this pattern. The fact that juvenile and adult skulls in birds do share a similar anatomical integration suggests the presence of specific constraint in their ontogenetic growth.
11P Practice patterns and 90-day treatment-related morbidity in early-stage cervical cancer
Authors: T. Golia D'Auge, V. Di Donato, A. Fracassi, I. Palaia, G. Perniola, L. Muzii, G. Scambia, P. Benedetti Panici, F. Raspagliesi, G. Bogani
Journal: Annals of Oncology (2022)
Systemic Treatment of Advanced Unresectable Hepatocellular Carcinoma after First-Line Therapy: Expert Recommendations from Hong Kong, Singapore, and Taiwan
Authors: Thomas Yau, David Tai, Stephen Lam Chan, Yi-Hsiang Huang, Su Pin Choo, Chiun Hsu, Tan To Cheung, Shi-Ming Lin, Wei Peng Yong, Joycelyn Lee, Thomas Leung, Tracy Shum, Cynthia S.Y. Yeung, Anna Yin-Ping Tai, Ada Lai Yau Law, Ann-Lii Cheng, Li-Tzong Chen
Journal: Liver Cancer (2022)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Asia has a high burden of hepatocellular carcinoma (HCC) due to the high rates of chronic hepatitis B infection and accounts for 70% of HCC cases globally. In the past 20 years, the systemic treatment landscape of advanced HCC has evolved substantially – from tyrosine kinase inhibitors to immune-oncology agents plus anti-vascular endothelial growth factor agents. The appropriate sequence of therapies has become critical in optimizing patient outcomes given the increase in systemic therapeutic options. This article evaluates the evidence and provides expert recommendations for the use of systemic therapies after first-line treatment in patients with advanced HCC. &lt;b&gt;&lt;i&gt;Summary:&lt;/i&gt;&lt;/b&gt; Based on three virtual meetings held in early 2021, a team of 17 experts comprising oncologists, a hepatologist, and a hepatobiliary surgeon from Hong Kong, Singapore, and Taiwan reviewed available data about systemic treatments for HCC after first line and formulated 28 statements. These statements aimed to provide expert guidance on selecting first and subsequent lines of therapies as well as recommending therapies in special circumstances, such as poor liver function, posttransplantation, recent gastrointestinal bleeding, or autoimmune diseases. Data supporting the statements were drawn from clinical trials and real-world studies. The 28 statements were then evaluated anonymously using a 5-point Likert scale, and 24 reached consensus, predefined as achieving 75% agreement. Statements generated covered the selection of first-line systemic therapy, considerations and goals of second-line systemic therapies, treatment selection following first-line therapy, and treatment recommendations following first-line tyrosine kinase inhibitors, immune-oncology monotherapy, or immune-oncology combination therapy. The authors also shared expert opinion on the use of second-line systemic therapy in patients with liver dysfunction, liver transplantation, and recent gastrointestinal or autoimmune disease. &lt;b&gt;&lt;i&gt;Key Messages:&lt;/i&gt;&lt;/b&gt; These expert statements summarize the latest data and expert opinion on selecting systemic treatment following first-line therapy in patients with unresectable advanced or metastatic HCC.
Association of the Patient Protection and Affordable Care Act With Ambulatory Quality, Patient Experience, Utilization, and Cost, 2014-2016
Authors: David M. Levine, Rohan Chalasani, Jeffrey A. Linder, Bruce E. Landon
Journal: JAMA Network Open (2022)

The Patient Protection and Affordable Care Act (ACA) expanded Medicaid eligibility at the discretion of states to US individuals earning up to 138% of the federal poverty level (FPL) and made private insurance subsidies available to most individuals earning up to 400% of the FPL. Its national impact remains debated.To determine the association of the ACA with ambulatory quality, patient experience, utilization, and cost.This cross-sectional study used difference-in-differences (DiD) analyses comparing outcomes before (2011-2013) and after (2014-2016) ACA implementation for US adults aged 18 to 64 years with income below and greater than or equal to 400% of the FPL. Participants were respondents to the Medical Expenditure Panel Survey, a nationally representative annual survey. Data analysis was performed from January 2021 to March 2022.ACA implementation.For quality and experience, this study examined previously published composites based on individual measures, including high-value care composites (eg, preventive testing) and low-value care composites (eg, inappropriate imaging), an overall patient experience rating, a physician communication composite, and an access-to-care composite. For utilization, outpatient, emergency, and inpatient encounters and prescribed medicines were examined. Overall and out-of-pocket expenditures were analyzed for cost.The total sample included 123 171 individuals (mean [SD] age, 39.9 [13.4] years; 65 034 women [52.8%]). After ACA implementation, adults with income less than 400% of the FPL received increased high-value care (diagnostic and preventive testing) compared with adults with income 400% or higher of the FPL (change from 70% to 72% vs change from 84% to 84%; adjusted DiD, 1.20%; 95% CI, 0.18% to 2.21%; P = .02) with no difference in any other quality composites. Individuals with income less than 400% of the FPL had larger improvements in experience, communication, and access composites compared with those with income greater than or equal to 400% of the FPL (global rating of health, change from 69% to 73% vs change from 79% to 81%; adjusted DiD, 2.12%; 95% CI, 0.18% to 4.05%; P = .03). There were no differences in utilization or cost, except that receipt of primary care increased for those with lower income vs those with higher income (change from 65% to 66% vs change from 80% to 77%; adjusted DiD, 2.97%; 95% CI, 1.18% to 4.77%; P = .001) and total out-of-pocket expenditures decreased for those with lower income vs those with higher income (change from $504 to $439 vs from $757 to $769; adjusted DiD, -$105.50; 95% CI, -$167.80 to -$43.20; P = .001).In this cross-sectional national study, the ACA was associated with improved patient experience, communication, and access and decreased out-of-pocket expenditures, but little or no change in quality, utilization, and total cost.
A macaque clonal hematopoiesis model demonstrates expansion of TET2-disrupted clones and utility for testing interventions
Authors: Tae-Hoon Shin, Yifan Zhou, Shirley Chen, Stefan Cordes, Max Z. Grice, Xing Fan, Byung-Chul Lee, Aisha A. Aljanahi, So Gun Hong, Kelli L. Vaughan, Julie A. Mattison, Steven G. Kohama, Margarete A. Fabre, Naoya Uchida, Selami Demirci, Marcus A.F. Corat, Jean-Yves Métais, Katherine R. Calvo, Manuel Buscarlet, Hannah Natanson, Kathy L. McGraw, Alan F. List, Lambert Busque, John F. Tisdale, George S. Vassiliou, Kyung-Rok Yu, Cynthia E. Dunbar
Journal: Blood (2022)
1P Comprehensive assessment of gene mutations revealed overlapping responses for PARPi and chemotherapy in ovarian cancer cells
Authors: A. Tozzi, R. Coelho, M. Disler, F. Lombardo, A. Fedier, M. Nunez Lopez, F. Freuler, F. Jacob, V. Heinzelmann-Schwarz
Journal: Annals of Oncology (2022)
Error in Figure 1
Journal: JAMA Network Open (2022)

Anne M. Butler, PhD; Derek S. Brown, PhD; Michael J. Durkin, MD, MPH; John M. Sahrmann, MA; Katelin B. Nickel, MPH; Caroline A. O’Neil, MA, MPH; Margaret A. Olsen, PhD, MPH; David Y. Hyun, MD; Rachel M. Zetts, MPH; Jason G. Newland, MD, MEd